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Related Experiment Video

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Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age.

Sílvia Llonch1, Montserrat Barragán2, Paula Nieto3

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Aging Cell
|April 28, 2021
PubMed
Summary

Advanced maternal age impacts the human oocyte transcriptome, particularly in mature oocytes (MII). Gene expression changes related to chromosome segregation and RNA splicing increase with age, potentially affecting fertility.

Keywords:
BMIadvanced maternal ageageingassisted reproductionfertilityhuman oocytesingle-cell RNA-Seqtranscriptomics

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Area of Science:

  • Reproductive biology
  • Genomics
  • Aging research

Background:

  • Female fertility declines with maternal age due to oocyte pool depletion and reduced developmental competence.
  • The impact of maternal age on the human mature oocyte (MII) transcriptome and its underlying pathways is not well understood.

Purpose of the Study:

  • To characterize and compare transcriptomes of germinal vesicle (GV) and in vitro matured (IVM-MII) oocytes across a range of maternal ages.
  • To identify age-related changes in gene expression within human oocytes.

Main Methods:

  • Transcriptome analysis of GV and IVM-MII human oocytes from women of varying reproductive ages.
  • Identification of stage-specific marker genes and age-dependent transcript alterations.
  • Gene regulatory network analysis to identify upstream regulators.

Main Results:

  • Two distinct cell clusters identified based on maturation stage (GV and IVM-MII) with numerous marker genes.
  • Maternal age significantly affected the transcriptome of IVM-MII oocytes (1219 genes) more than GV oocytes (596 genes).
  • Increased transcript representation with age was observed for genes involved in chromosome segregation and RNA splicing; mitochondrial activity genes showed decreased representation.

Conclusions:

  • Advanced maternal age does not globally alter the oocyte transcriptome at GV or IVM-MII stages.
  • Hundreds of genes show altered transcript representation, especially in IVM-MII oocytes, potentially contributing to age-related oocyte quality decline.
  • Gene regulatory network analysis identified potential master regulators of age-related transcriptomic changes.